Diabetes uniquely impacts all components of the erectile response, and all co-morbid medical conditions, imparts the greatest risk of ED. In that population based analysis of OS men aged 20 and up, 49% of all men with diabetes reported ED. Furthermore, men with diabetes utilize more health care resources for ED treatment than men without diabetes, and the incidence of diabetes if increasing. In addition to the increased prevalence of ED in the diabetic population, the onset of ED in this cohort is up to 10-15 years earlier than in the g~neral population. This is particularly relevant because younger men are more likely to seek care and utilize health care resources for the treatment of ED. Thus, interventions to improve or prevent ED in men with diabetes will become increasingly important. To test our general hypothesis that increased tissue specific penile expression of ceruloplasmin in diabetes results in impaired cavernosal vasodilation and penile endothelial dysfunction, we will complete the following specific aims: (1) determine if ceruloplasmin inhibits NO bioavailability through the inhibition of eNOS activity, 2) determine the role of ceruloplasmin on penile vascular endothelial function in vivo, 3) investigate whether ceruloplasmin causes impaired penile erection in a mouse model of type 1 diabetes. Relevance to Public Health: Treatment or prevention of ED in men with diabetes is necessary to improve life satisfaction and reduce the utilization of health care resources in this rapidly growing portion of the American population. Relevance to Public Health: Treatment or prevention of ED in men with diabetes is necessary to improve life satisfaction and reduce the utilization of health care resources in this rapidly growing portion of the American population. [unreadable] [unreadable] [unreadable]